Abstract
This study presents the results of DNA methylation analysis in different regions of the ascending aorta (dilated, non-dilated area, atherosclerotic plaque) in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation levels between dilated and normal aortic tissues were detected for two CpG sites of the NR2F1-AS1 gene (|Δβ| ≥ 0.2 and FDR 0.05). Between atherosclerotic plaque samples and dilated/normal aortic tissues, 586/480 differentially methylated CpG sites (DMSs) were identified, among which 323/234 were hypermethylated and 263/246 were hypomethylated in atherosclerotic plaques. DMSs were located mainly in introns and intergenic regions, 88.2% in the binding sites of TFs, among which ZNf263, ZFP148, PATZ1, NRF1, TCF12, EGR1 play a role in the pathogenesis of atherosclerosis of various arteries, and ELK1, ETS1, KLF15 play a role in aortic aneurysms. Sixteen DMSs are located in the region of genes (CMIP, RPH3AL, XRCC1, GATA5, EXD3, KCNC2, HIVEP3, ADCY9, CDCP2, FOLR1, WT1, MGMT, GAS2, CA1, PRSS16, ANK3) whose protein products are involved in the development of both aortic dissection and atherosclerosis in different arterial circulation regions. The protein products of these genes are involved in a wide range of biological processes, including mesenchyme development (GO:0060485, FOLR1, WT1, GATA5, HIVEP3, KCNC2) and positive regulation of DNA metabolic process (GO:0051054, MGMT, WT1, XRCC1).
Published Version
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